The present invention relates to the field of containers for holding medical fluids for administration to patients. As used herein the term “medical fluids” includes medical, biological and veterinary fluids. Thus the “patients” could be humans, fish, animals, reptiles, amphibians, birds, etc. More particularly, the present invention relates to flexible autoclavable intravenous (IV) fluid containers or bags and non-PVC polyolefin film for their construction. The invention provides long shelf life flexible IV fluid containers that have a low moisture vapor transmission rate and can be terminally sterilized using high temperature treatment, i.e., sterilized after filling to deactivate microorganisms inside the containers (e.g., autoclaving).
Over thirty years ago, the introduction of a flexible IV container raised the issue of water loss and port closure system integrity testing. The selection of a flexible container material system and suitable port closures had to be designed. The most common design selected was some sort of PVC mono-layer film container with a very low cost closure system. Placing another material with higher barrier properties as an overwrap around the filled container solved the issue of the water loss during shelf life. The entire system would then be steam sterilized and delivered to the customer for use.
Polyvinyl Chloride (PVC) is a standard, widely used plastic packaging material used to manufacture flexible containers (bags and pouches) for the administration of small volume parenterals (SVP), often referred to as mini-bags; large volume parenterals (LVP); and various enteral nutritional and liquid preparations. These containers are often utilized for patient hydration and/or to supply pharmaceutical preparations, medicines, vitamins, nutritionals, and the like. Heretofore, PVC has proven to be advantageous because of its resistance to heat, which allows the containers to be terminally sterilized using high temperature treatment.
However, PVC also has its shortcomings. PVC films in the thickness range needed to be acceptably flexible for IV fluid containers typically do not provide a high moisture vapor barrier (MVB). The moisture vapor transmission rate (MVTR) of flexible PVC containers is so high that an overwrap is required to increase the shelf life of the fluids contained therein by providing improved moisture vapor barrier (MVB) properties, as compared to the MVB properties of PVC alone. In other cases, an overwrap is used to contain any leakage and help the port system of the flexible containers to survive autoclaving (i.e., high temperature treatment) or shipping and handling damage. In some cases, and particularly for SVP packages (or bags), multiple SVP packages are placed into one overwrap package. Disadvantageously, once the one overwrap package has been opened, the shelf life of the individual SVP packages contained therein is limited to approximately 30 days, because of the poor MVB properties of PVC. Thus, if a practitioner opens an overwrap containing SVPs, but does not use all of the SVPs in a timely manner, the SVP packages must be discarded approximately 30 days after the overwrap is opened. The overwrap represents added packaging cost and weight, contributes to environmental waste, and depletes petroleum and other resources.
As time passed and new materials and technologies were brought to the pharmaceutical industry, laminated materials typically including three or more layers have come to the forefront for use in IV flexible containers. These laminated materials incorporate an integrated overwrap type film layer to provide the flexible IV container with similar water vapor protection as the separate overwrap system.
To perform well, an intravenous medical fluid container must: 1) drain uniformly, preferably with a readable falling meniscus; 2) have minimal air volume so that patient air embolisms are not an issue; and 3) leave minimal residual volume upon draining so the patient accurately receives the prescribed amount of drug or fluid. Only if the container is flexible, can all of these objectives can be met simultaneously. A flexible container, as the term is used herein, means a container that collapses upon draining, such as a bag for example. Rigid containers, of course, do not change shape substantially upon draining. Semi-rigid containers have substantially the same shape in a filled state and in a drained state, i.e., they may deform some while draining but do not permanently collapse without application of external forces when drained. Semi-rigid containers or plastic bottles also require significant amounts of included air or venting to drain properly. Anyone who has poured milk from a semi-rigid plastic container or oil from a semi-rigid can will appreciate that semi-rigid containers tend to drain sporadically and often unpredictably unless properly vented. Undesirable reversing of flow or suctioning can occur with semi-rigid containers. Heretofore, flexibility has been pursued in conventional intravenous fluid containers by making the material or film of the bag or container very thin (i.e., on the order of a few mils), using a material with a very low modulus of elasticity, or both. However, low modulus or thin films tend to melt at temperatures lower than typical US or European autoclave temperature requirements, and have an undesirably high moisture vapor transmission rate such that an overwrap is required for each container.
Materials other than PVC, such as polyolefins (e.g., polyethylene or polypropylene), nylon, or a composite material, either laminated or co-extruded structure (including both monolayer and multilayer structures), and the like, have been proposed for SVP and/or LVP. One advantage is to reduce or eliminate the use of PVC because of environmental concerns. Another advantage of materials such as polypropylene or polyethylene is that they have better MVB properties than PVC. However, manufacturers and regulatory agencies have been hesitant to eliminate overwraps due to concerns regarding sterility and possible handling damage to and/or leakage from port closure system of polyolefin flexible medical fluid containers. Reliable, economical, longer shelf life, lower moisture vapor transmission rate flexible medical fluid containers have yet to be realized due to port closure deficiencies, the multitude of materials to be selected and/or blended, as well as the many, often conflicting design constraints that must be met. Among these constraints are cold impact strength for “drop tests”, capability to withstand the high heat autoclave cycles required in the United States and Europe, USP requirements, drug concentration and assay requirements, allowed fill volume, filling equipment and manufacturing process tolerances, aesthetic appearance (clarity, gloss, haze, wrinkling), printability, drainability, and types and levels of extractables permitted.
Another advantage to replacing PVC with a material such as polypropylene or polyethylene is that products such as pure deionized water (U.S.P. for injection) cannot be effectively packaged in PVC because by-products from the PVC packaging material leach into the pure deionized water, contaminating it, whereas materials such as polyolefins can be formulated so as not to contain by-products that leach into the pure deionized water.
Access ports are commonly used in infusion solution containers to administer solutions to a patient, or to add medicaments or other solutions to the container prior to administration. Current solution containers typically may include a dedicated outlet port for solution administration to a patient and a dedicated inlet port for the addition of diluent or other ingredients to the container.
The outlet port is intended to be coupled to an administrative set and is therefore commonly referred to as the administrative port, whereas the inlet port is designed to permit the injection of therapeutic agents and nutrients into the partially filled container and is sometimes identified as the additive port. Such a container may contain a partial filling of a sterile solution such as saline or dextrose to function as a diluent for the injected additive. Alternatively, the container may house the drug and the diluent can be added by injection into the container through the additive port. The diluted drug or nutrient is then administered to a patient by means of the administrative port and an administrative set that may be either directly or indirectly (i.e., through another solution set) coupled to the patient. Strict limits or tolerances are often imposed on the assay or concentration of the drug to be delivered. Meeting these limits, especially if the filled container is stored for an extended period of time, is difficult if the moisture barrier of the container is too high.
Therefore, an object of this invention is to provide an improved medical fluid container.
A further object of the invention is to provide containers with port closure assemblies that improve the safety and ease of handling when fluids are to be withdrawn or introduced.
Another object of the invention is to provide a port fill tube configuration that increases container sealing reliability, as well as the ease and efficiency of manufacture.
A further object of the invention is to provide a container with container wall formed of a multiple layer polyolefin material selected so as to meet the demanding requirements for terminally sterilized IV containers.
A further object of the invention is to provide an improved method of fabricating and filling medical fluid.
A further object of the invention is to provide an improved method of packaging and storing medical fluid containers.
These and other objects will be apparent to those skilled in the art.